Deuterated derivatives of psilocybin and uses thereof

Abstract

Provided herein are pharmaceutical compositions comprising deuterated derivatives of psilocybin. The provided compositions may be useful for treating and/or preventing various diseases and conditions, such as mood or psychiatric disorders.

What is claimed is: 
     
         1 . A method of treating a neurological or psychiatric disorder in a subject in need thereof, the method comprising administering an effective amount of a pharmaceutical composition comprising a deuterated compound of Formula (IA-2) or (IA-3): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, prodrug, hydrate, or solvate thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the disorder is a psychiatric disorder. 
     
     
         3 . The method of  claim 2 , wherein the psychiatric disorder is a depressive disorder or an eating disorder. 
     
     
         4 . The method of  claim 3 , wherein the depressive disorder is major depressive disorder or treatment-resistant depression. 
     
     
         5 . The method of  claim 1 , wherein the disorder is a neurological disorder. 
     
     
         6 . The method of  claim 5 , wherein the neurological disorder is a pain disorder. 
     
     
         7 . The method of  claim 1 , wherein the composition comprises the deuterated compound of Formula (IA-2) or (IA-3), or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The method of  claim 7 , wherein the composition comprises about 0.5 mg to about 50 mg of the deuterated compound of Formula (IA-2) or (IA-3), or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 7 , wherein the composition comprises about 10 mg to about 50 mg of the deuterated compound of Formula (IA-2) or (IA-3), or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         11 . The method of  claim 10 , wherein the composition is administered orally. 
     
     
         12 . The composition of  claim 11 , wherein the composition is a solid dose composition. 
     
     
         13 . The method of  claim 12 , wherein the composition is a tablet, capsule, granule, powder, sachet, or chewable. 
     
     
         14 . The method of  claim 10 , wherein the composition is administered intravenously. 
     
     
         15 . The method of  claim 14 , wherein the composition comprises about 0.01 mg/ml to about 50 mg/ml of the deuterated compound of Formula (IA-2) or (IA-3), or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 1 , wherein the subject is a human subject. 
     
     
         17 . The method of  claim 1 , wherein the plasma half-life (t1/2) of the deuterated compound is at least 5%, 10%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60% longer than an equivalent dose of a non-isotopically enriched compound having the same structure as the compound. 
     
     
         18 . The method of  claim 1 , wherein the administration of the deuterated compound results in at least a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% reduction in the formation of the psilocin-O-glucuronide metabolite compared to an equivalent dose of a non-isotopically enriched compound having the same structure as the compound. 
     
     
         19 . The method of  claim 1 , wherein the administration of the deuterated compound results in the reduction of one or more side effects compared to the administration of its natural (non-isotopically enriched) counterpart at an equivalent dose. 
     
     
         20 . The method of  claim 1 , wherein the one or more side effects is derealization, visual alteration, visual distortion, dilated pupils, dizziness, drowsiness, impaired concentration, muscle weakness, lack of coordination, unusual body sensations, nausea, paranoia, confusion, hallucinations, nausea or vomiting, yawning, increased blood pressure (systolic), increased blood pressure (diastolic) or increased heart rate.